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CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection.

Komuro I, Yokota Y, Yasuda S, Iwamoto A, Kagawa KS - J. Exp. Med. (2003)

Bottom Line: Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication.Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate.These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.

ABSTRACT
Granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced monocyte-derived macrophages (GM-MPhi) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MPhi) produce a large amount of HIV-1. M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta. GM-MPhi express a high level of C/EBPbeta and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPbeta but decreases that of Hck. Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication. Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.

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Immunoblot analysis of C/EBPβ in M-MΦ and GM-MΦ. (A) Immunoblots of C/EBPβ protein in PBMC, PHA-activated CD4+ T cells, Mo, and Mo-derived MΦs. (B) Immunoblots of C/EBPβ protein in HIV-1BaL–infected M-MΦ and GM-MΦ at 2 d PI. The relative amounts of the large band to the small band (L/S ratio) of C/EBPβ were calculated using PSL values of 37 kD and 23 kD of C/EBPβ isoforms. The data shown here are representative one of three independent experiments.
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fig3: Immunoblot analysis of C/EBPβ in M-MΦ and GM-MΦ. (A) Immunoblots of C/EBPβ protein in PBMC, PHA-activated CD4+ T cells, Mo, and Mo-derived MΦs. (B) Immunoblots of C/EBPβ protein in HIV-1BaL–infected M-MΦ and GM-MΦ at 2 d PI. The relative amounts of the large band to the small band (L/S ratio) of C/EBPβ were calculated using PSL values of 37 kD and 23 kD of C/EBPβ isoforms. The data shown here are representative one of three independent experiments.

Mentions: Previous studies indicate that large isoform and short isoform of C/EBPβ stimulates and inhibits the HIV-1 replication in MΦ, respectively (21, 23). To investigate the possibility that the difference in the expression of the C/EBPβ isoforms correlates with the distinct susceptibility to HIV-1 replication in M-MΦ and GM-MΦ, we examined the expression of C/EBPβ isoforms in M-MΦ and GM-MΦ before and after HIV-1 infection by immunoblots. Before HIV-1 infection, the levels of C/EBPβ protein in GM-MΦ were much higher than that in M-MΦ. The small isoform (23 kD) was especially detectable in GM-MΦ but not in M-MΦ, and the relative amounts of the large band (37 kD) to the small band (23 kD; L/S ratio) of C/EBPβ in M-MΦ and GM-MΦ were 13.3 ± 0.78 and 1.32 ± 0.13, respectively (Fig. 3 A). In contrast to these MΦs, both PBMCs and Mo showed very low level expression of C/EBPβ, and the expression of C/EBPβ in PHA-activated CD4+T cells resembled that of M-MΦ.


CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection.

Komuro I, Yokota Y, Yasuda S, Iwamoto A, Kagawa KS - J. Exp. Med. (2003)

Immunoblot analysis of C/EBPβ in M-MΦ and GM-MΦ. (A) Immunoblots of C/EBPβ protein in PBMC, PHA-activated CD4+ T cells, Mo, and Mo-derived MΦs. (B) Immunoblots of C/EBPβ protein in HIV-1BaL–infected M-MΦ and GM-MΦ at 2 d PI. The relative amounts of the large band to the small band (L/S ratio) of C/EBPβ were calculated using PSL values of 37 kD and 23 kD of C/EBPβ isoforms. The data shown here are representative one of three independent experiments.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194092&req=5

fig3: Immunoblot analysis of C/EBPβ in M-MΦ and GM-MΦ. (A) Immunoblots of C/EBPβ protein in PBMC, PHA-activated CD4+ T cells, Mo, and Mo-derived MΦs. (B) Immunoblots of C/EBPβ protein in HIV-1BaL–infected M-MΦ and GM-MΦ at 2 d PI. The relative amounts of the large band to the small band (L/S ratio) of C/EBPβ were calculated using PSL values of 37 kD and 23 kD of C/EBPβ isoforms. The data shown here are representative one of three independent experiments.
Mentions: Previous studies indicate that large isoform and short isoform of C/EBPβ stimulates and inhibits the HIV-1 replication in MΦ, respectively (21, 23). To investigate the possibility that the difference in the expression of the C/EBPβ isoforms correlates with the distinct susceptibility to HIV-1 replication in M-MΦ and GM-MΦ, we examined the expression of C/EBPβ isoforms in M-MΦ and GM-MΦ before and after HIV-1 infection by immunoblots. Before HIV-1 infection, the levels of C/EBPβ protein in GM-MΦ were much higher than that in M-MΦ. The small isoform (23 kD) was especially detectable in GM-MΦ but not in M-MΦ, and the relative amounts of the large band (37 kD) to the small band (23 kD; L/S ratio) of C/EBPβ in M-MΦ and GM-MΦ were 13.3 ± 0.78 and 1.32 ± 0.13, respectively (Fig. 3 A). In contrast to these MΦs, both PBMCs and Mo showed very low level expression of C/EBPβ, and the expression of C/EBPβ in PHA-activated CD4+T cells resembled that of M-MΦ.

Bottom Line: Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication.Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate.These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.

ABSTRACT
Granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced monocyte-derived macrophages (GM-MPhi) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MPhi) produce a large amount of HIV-1. M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta. GM-MPhi express a high level of C/EBPbeta and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPbeta but decreases that of Hck. Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication. Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.

Show MeSH
Related in: MedlinePlus